Monthly Archives: March 2023

The Physiology of the G.O.A.T. (Part 1- endocrine)

Who is the G.O.A.T.?

Figure 1 shows the main life events that took place since the G.O.A.T. was born. Lionel Andres Messi Cuccittini (Leo) was born on the 24th of June 1987, in the city of Rosario, Santa Fé province, Argentina. In 1992, when he was 4 years old, his grandmother suggested that he should play for local club “Abanderado Grandoli”. Even at that young age, his agility and soccer skills were quickly noticed, and he signed into the historic professional soccer team in Rosario, called Newell’s Old Boys, in the youth ranks in 1995. Newell’s Old Boys is notorious for being one of the few professional clubs from outside of Buenos Aires, Argentina, that has dominated the national scenes of the sport. Many great Argentinean players and tacticians have emerged from this club.

In 1998, unfortunate news came to Leo with his diagnosis of growth hormone deficiency (GHD), he immediately started the treatment, but his family struggled to find the means to pay for the treatment. Regardless, he continued to play soccer, and his father, continued looking for a club for Messi, as his talent was very evident. A scout from Barcelona, Spain, received a tip about a boy in Argentina called Messi. He had been watching videos of this player and knew about the need of the young player for GHD treatment, but everybody thought he was too young and little (2). Nevertheless, because of Messi’s extraordinary skills, a trial for the 11-year-old was arranged in Barcelona. The scout, and everybody present, were surprised to see the talented, and unusually small 11- year-old playing a game, and tried to sign him immediately. However, there was a delay that felt like an eternity, and Messi’s father told Barcelona’s scout that they needed to return to Argentina, and they couldn’t keep waiting for a decision. And right there, the scout was in such a rush to sign Messi that he wouldn’t wait to have a written contract, and did not want to lose such talent, so they signed an agreement on a napkin (  In 2000, Messi joined “La Masia, FC Barcelona’s youth academy” and Messi and his father moved to Spain. Part of the contract included paying for Messi’s GHD treatment.

Messi made his debut with Barcelona in 2004, against city rivals Espanyol. Two years later, in 2006, Messi played at his first World Cup for Argentina. Two years after that, he won the Olympic gold medal with Argentina at the 2008 Beijing Olympics. By 2009, Leo had proven his mettle, and was voted the FIFA’s Ballon d’Or winner, the best player in the world, and received this prestigious award six more times. In 2022, Messi achieved his lifelong dream, and won the world cup with Argentina, and unofficially became the G.O.A.T. In early March 2023, Messi was voted yet again as the FIFA best men’s player, in other words, now Messi is “officially” the G.O.A.T.

Size matters, but it is not the main problem!

Messi was 1.32m (4ft 4in) tall at the age of 11 and he had not grown in a couple of years [1]. So, yes height was an issue, but not the biggest issue. Messi suffered from growth hormone deficiency-GHD. According to the Endocrine Society, GHD is a rare condition affecting 1 in 4,000- 1in 10,000 cases [2], and unfortunately, Messi was one of these rare cases. When children have GHD the normal growth of bone and muscle is impaired. GHD can be congenital or acquired, but the consequences of it go well beyond the obvious slowing in growth and short stature. It can cause serious systemic problems, including glucose [3] and fat metabolism [4], cardiovascular complications [5], depression [6], and all of these also lead to fatigue and  exercise intolerance.

Figure 3 illustrates how the secretion of GH occurs, and its actions on various target organs. Under normal healthy conditions, there is a fluctuation in GH secretion during the day, with a marked increase in its secretion during sleep, most precisely about an hour after the onset of deep sleep. Inputs such as exercise, stress, hypoglycemia signal the hypothalamus to secrete growth hormone releasing hormone (GHRH), this hormone travels to the anterior pituitary gland where ultimately, GH is secreted.  Somatropes are the cells in the anterior pituitary gland that secrete GH, which travels systemically to the liver, where insulin-like growth factor 1 is secreted (IGF-I). IGFs act on target cells that cause growth of bone and soft tissues. Since Messi had GHD, the levels of IGF-I were probably lower, slowing his growth during pre-pubertal years before the growth spurt. Other factors affect the levels of IGF-I, most specifically, inadequate nutrition negatively affects its levels in the blood. Fortunately, Messi received treatment before puberty, allowing him to grow to be 170 cm tall (5’7”). However, not only the lack of growth in bone and soft tissues could have halted his amazing athletic career, GHD also results in metabolic complications not related to growth that could have affected his tolerance to exercise.

Give me the sugar!

As illustrated in figure 3, GH acts directly on skeletal muscle, the liver, and adipose tissue. The overall action of GH is to maintain glucose homeostasis. In other words, GH increases the levels of circulating blood glucose, critical to produce adenosine triphosphate (ATP) for energy at rest, and most importantly during exercise. The action of GH on the muscle is to inhibit the glucose uptake by the muscle, thus, increasing the levels of circulating glucose to be later used for ATP production. Additionally, to further spare glucose in the blood stream, GH mobilizes fat stores by breaking down triglycerides, increasing fatty acid levels in blood. In the liver, GH also promotes gluconeogenesis, or the formation of glucose from non-carbohydrate substrates. All these actions can occur simultaneously and depend on the intensity and duration of exercise. With GHD, athletes can be more easily fatigued, and Messi probably would have been unable to perform to the level he did, and becoming the G.O.A.T.

We need glucose to create ATP, during exercise, especially at high intensities as humans depend on the ability to spare glucose, the only fuel for the central nervous system. Your brain is like a selfish boss, everybody (in this case every organ) must work to keep it happy and functioning. To keep your brain “happy” the rest of your organs need to make sure enough glucose is in the blood for the brain to have the energy for all of its intricate functions.

This glucose homeostasis happens by the orchestrated actions of several hormones including glucagon, cortisol, catecholamines and GH. One of the major adaptations of training is the decrease reliance on carbohydrates for energy and a shift to fat metabolism. At rest and low intensity exercise, we use mostly fats as “fuel” however, when we go above 50-60% of the maximum, we switch to carbohydrates for metabolism. This phenomenon is called the “crossover point”. Endurance exercise training shifts this crossover point to higher intensities, sparing glucose and decreasing the accumulation of lactic acid. When a person exercises and experience the “hit the wall” phenomenon (i.e., the sudden loss of energy during an endurance event like a race) it is due to low blood glucose levels. GHD probably could have played a role on Messi’s metabolism if not treated.

What else makes the G.O.A.T the best?

There is much to talk about Messi, from the endocrine system to his extraordinary neural activity that makes him very fast and coordinated. From his tolerance to fatigue, high maximal oxygen consumption and lactate threshold to the muscle fiber type to motor unit recruitment and synchronization, we are going to focus only on the metabolic adaptations of training of this elite athlete, and we promise a part 2 of this blog post to talk about the rest of the adaptations of training that makes the G.O.A.T the best!

Maximal Oxygen Consumption (VO2max)

Oxygen consumption refers to the amount of oxygen being taken up by the tissues per minute to oxidize substrates (like carbohydrates and fats). Maximal oxygen consumption (or VO2max) refers to the amount of oxygen used during an incremental exercise to exhaustion. The higher the VO2max the higher the endurance capacity of the person, and their “fuel” utilization. This oxygen is being taken up by skeletal muscle and used in the mitochondria to create ATP. One adaptation of endurance training is having higher VO2max values. While sedentary males range between 25- 45 ml/kg/min, and distance runners could be between 65- 85 ml/kg/min,  the values for professional soccer players can range between 59.2 to 63.2 ml/kg/min, and mid-fielders and attackers have higher values than defenders and goalies [7].

A limitation of this test is that it is conducted in standardized conditions in a laboratory, and fails to replicate the actual consumption, often supra-maximal, that occurs during a game. Nevertheless, this is the gold standard measurement for cardiovascular fitness, and we speculate that the G.O.A.T. may have high VO2max values. We also think that Messi has a high lactate threshold, or the point in which lactate production exceeds clearance during this incremental maximal exercise test to exhaustion. High lactate threshold and crossover point can be related, as the endurance-trained person has better ability to spare glucose (carb reserves) and thus creates less lactic acid. Also, higher oxidative metabolism results in higher ability to oxidize lactate during the athletic event and use it as fuel.  Athletes like Messi usually have all the biochemical adaptations that make their skeletal muscle fibers more resistant to fatigue. This is due to mitochondrial proliferation and capillary recruitment. Messi is also a very explosive and fast player, due to a combination of nature (his genetic makeup) and nurture (his training), probably with a high number of Type II fast-oxidative muscle fibers with high levels of Myosin-ATPase activity. These fibers have intermediate resistance to fatigue, high oxidative phosphorylation capacity, fast speed of contraction, many capillaries and mitochondria and high myoglobin content.

Why is Messi the G.O.A.T?

The chances of a young boy from the countryside of Argentina with GHD to be even considered for any major international soccer club are very slim. This is because in Argentina everybody plays soccer and there are numerous soccer players and too much competition. In fact, Messi was rejected from giant club “River Plate” in Buenos Aires, Argentina, before signing his agreement on a napkin with Barcelona.  The economic disparities also play a role on the odds of any young player to become a professional soccer player if any medical treatment is needed. However, there was something special about this boy, and it only took a trained eye to envision a wonderful professional career. Without the hormonal supplementation, Messi would have probably never had a shot. Fortunately for soccer fans all over the world, advances in biomedical research made it possible for Messi to reach his full potential and become this phenomenon adored by all.


  1. Hawkey, I. Lionel Messi on a mission. 2008 [cited 2023 March 5]; Available from:
  2. Endocrine_Society. Growth Hormone Deficiency. 2023 [cited 2023 March 6th]; Available from:
  3. Hew, F.L., et al., Growth hormone deficiency and cardiovascular risk. Baillieres Clin Endocrinol Metab, 1998. 12(2): p. 199-216.
  4. Gertner, J.M., Growth hormone actions on fat distribution and metabolism. Horm Res, 1992. 38 Suppl 2: p. 41-3.
  5. Lombardi, G., et al., The cardiovascular system in growth hormone excess and growth hormone deficiency. J Endocrinol Invest, 2012. 35(11): p. 1021-9.
  6. Karachaliou, F.H., et al., Association of growth hormone deficiency (GHD) with anxiety and depression: experimental data and evidence from GHD children and adolescents. Hormones (Athens), 2021. 20(4): p. 679-689.
  7. Slimani, M., et al., Maximum Oxygen Uptake of Male Soccer Players According to their Competitive Level, Playing Position and Age Group: Implication from a Network Meta-Analysis. J Hum Kinet, 2019. 66: p. 233-245.
Benjamin Puppato is a junior in the International Baccalaureate program at Floyd Central High School. He loves playing soccer, and also he is interested in statistics and facts about soccer, particularly of Argentinean players and teams.





Dr. Terson de Paleville is an associate professor of Physiology at the University of Louisville’s School of Medicine. She teaches Exercise Physiology and Human Physiology courses. Dr. Terson de Paleville has investigated the effects of activity-based therapy on respiratory muscles, body composition and autonomic function after spinal cord injury. Additional research project involves research on best practices for teaching physiology.

“Is integrated curriculum disintegrating the holistic approach among smart learners?”

I feel smart learners are becoming surface learners in the integrated curriculum by juggling with only the learning outcomes included in the blueprint without processing the information. They calculate the bare minimum content required just to pass. They are not ready to come out of their comfort zone to progress by acquiring hard-core concepts at the level of application and synthesis. They appear in a module exam and stop relating it to other modules.

Integrated curriculum is being implemented at the cost of lack of ownership by subject specialists. System-based modules lay the foundation of disciplines on Anatomy but not on the themes associated with clinical features like chest pain. When diseases are studied within systems, the integration is itself disintegrated into anatomical boundaries.

Problem-based learning from which students can derive their own learning outcomes to solve the scenario remains the only hope to integrate the systems, as diseases seldom restrict themselves to one system. As assessment drives learning, PBL may be assessed by case-cluster-MCQs and integrated viva by relevant subject specialists. Being a student-centered methodology, adding to the burden of an integrated curriculum involving multiple subjects, PBL is usually neglected by the student body. There is a dire need to innovate PBL and make it interesting by using students as simulated patients and by allowing them into doctor-patient-role-play, whereas the remaining students may be engaged in healthy critique and feedback along with critical thinking, leadership and teamwork to achieve academic as well as social learning. PBL workshops with faculty and students may be beneficial.

The relatively new concept of “patients as educators of students” may be practiced by recruiting actors and real patients carefully through interviews and seeking their consent for history-taking and/or physical examination. Feedback and assessment by simulated patients may contribute to real-patient safety. Their video may be created as a future learning resource. Smart learners need smart teachers to handle them along with their modern curriculum.

Prof. Dr. Samina Malik

HOD Physiology, University College of Medicine and Dentistry, The University of Lahore

PBL Country head for Pakistan, Asia-Pacific Association on PBL in Health Sciences (APA-PHS)

Secretary General, South Asian Association of Physiologists

Masters in Med Edu student at Dundee university, UK

Member APS, Teaching of Physiology section (Member No. 00307332)